The Section on Molecular Neuroscience studies the molecular mechanisms of chemically coded ionotropic and metabotropic neurotransmission in in the nervous system. The ultimate goals of the project are identifying signal transduction pathways and trans-acting factors that uniquely control late nervous system phenotypic development, discovering new mammalian neurotransmitters and receptors through examination of the molecular evolution of neurotransmission, and developing ways to understand and restore neurotransmitter balance in animal models of human CNS disease. The following work is in progress in our laboratory:1. Characterization of the ubiquitous secretory protein chromogranin A as a vesiculogenic factor for the generation of large dense-core vesicles (LDCVs) in neuroendocrine cells.2. Development of a neuropeptide-deficient mouse to study the role of classical neurotransmitter-neuropeptide co-transmission through parallel release from small synaptic vesicles (SSVs) and LDCVs in the same peripheral neuron.3. Discovery of a combinatorial signaling system activated by the neuropeptide PACAP that targets the VIP gene in neuroendocrine cells through two novel pathways involving calcineurin and cAMP-dependent/protein kinase A-independent signaling, respectively. 4. Characterization of the unique co-expression of prostaglandin synthetic enzymes in cholinergic neurons of the primate, compared to the rodent, cholinergic projection neurons of the nucleus basalis of Meynert.